Studies in humans have indicated that aldosterone excess induces left ventricular (LV) hypertrophy independent of hypertension. Ultrasonographic studies further suggest that myocardial hypertrophy due to hyperaldosteronism occurs concomitantly with myocardial fibrosis. The importance of these findings is highlighted by our recent observation that primary aldosteronism (PA) is several times more prevalent in patients with resistant hypertension than previously thought. Interestingly, in patients with resistant hypertension, chronic blockade of the renin-angiotensin system (RAS) does not attenuate LV hypertrophy in PA patients relative to non-PA patients despite a similar blood pressure reduction. The central role of aldosterone in promoting perivascular inflammation and fibrosis in the heart independent of blood pressure has been confirmed in experimental models of hyperaldosteronism. This pro-fibrotic action is blocked not only by mineralocorticoid receptor antagonism but also by a low-salt diet. This important observation as well as the general relation between NaCl and aldosterone to LV remodeling remains to be elucidated in humans. We hypothesize that aldosterone-induced myocardial fibrosis is primarily an inflammatory process that depends highly on the dietary salt status. To test this hypothesis we will: Specific Aim 1) To show that in humans, aldosterone excess causes LV hypertrophy and fibrosis through inflammatory pathways, we will relate markers of inflammation and oxidative stress to LV hypertrophy and fibrosis in PA patients; Specific Aim 2) We expect that spironolactone will reverse cardiac hypertrophy in PA patients. However, in this aim, we will examine if spironolactone-dependent reverse-LV remodeling relates to markers of inflammation and/or cardiac fibrosis in these patients; Specific Aim 3) Show that dietary salt restriction reduces myocardial fibrosis, inflammation, and oxidative stress in patients with PA; Specific Aim 4) Using genetic models and pharmacologic approaches, show a cause-and-effect relation between aldosterone-induced inflammation and subsequent cardiac fibrosis. If these proposed studies show that inappropriately high aldosterone secretion relative to dietary salt ingestion causes adverse cardiac remodeling, a new paradigm would be created in which the "aldosterone-salt product" predicts cardiovascular risk.